title: NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation.
abstract: Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affecting maternally methylated germline differentially methylated regions (gDMRs), suggesting that NLRP7 plays an important role in reprogramming imprinted gDMRs. How NLRP7-a component of the CATERPILLAR family of proteins involved in innate immunity and apoptosis-causes these specific DNA methylation and trophoblast defects is unknown. Because rodents lack NLRP7, we used human embryonic stem cells to study its function and demonstrate that NLRP7 interacts with YY1, an important chromatin-binding factor. Reduced NLRP7 levels alter DNA methylation and accelerate trophoblast lineage differentiation. NLRP7 thus appears to function in chromatin reprogramming and DNA methylation in the germline or early embryonic development, functions not previously associated with members of the NLRP family.
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Mahadevan
authors.forename: Shu
authors.initials: S
authors.lastname: Wen
authors.forename: Ying-Wooi
authors.initials: YW
authors.lastname: Wan
authors.forename: Hsiu-Huei
authors.initials: HH
authors.lastname: Peng
authors.forename: Subhendu
authors.initials: S
authors.lastname: Otta
authors.forename: Zhandong
authors.initials: Z
authors.lastname: Liu
authors.forename: Michelina
authors.initials: M
authors.lastname: Iacovino
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Mahen
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: Bekim
authors.initials: B
authors.lastname: Sadikovic
authors.forename: Ignatia B
authors.initials: IB
authors.lastname: Van den Veyver
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008969:Molecular Sequence Data; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; C502448:NLRP7 protein, human; D050986:YY1 Transcription Factor; C494698:YY1 protein, human